Optimization of critical quality attributes in continuous twin-screw wet granulation via design space validated with pilot scale experimental data

Abstract

In this study, the influence of key process variables (screw speed, throughput and liquid to solid (L/S) ratio) of a continuous twin screw wet granulation (TSWG) was investigated using a central composite face-centered (CCF) experimental design method. Regression models were developed to predict the process responses (motor torque, granule residence time), granule properties (size distribution, volume average diameter, yield, relative width, flowability) and tablet properties (tensile strength). The effects of the three key process variables were analyzed via contour and interaction plots. The experimental results have demonstrated that all the process responses, granule properties and tablet properties are influenced by changing the screw speed, throughput and L/S ratio. The TSWG process was optimized to produce granules with specific volume average diameter of 150 μm and the yield of 95% based on the developed regression models. A design space (DS) was built based on volume average granule diameter between 90 and 200 μm and the granule yield larger than 75% with a failure probability analysis using Monte Carlo simulations. Validation experiments successfully validated the robustness and accuracy of the DS generated using the CCF experimental design in optimizing a continuous TSWG process.

Development of a Resveratrol Nanosuspension Using the Antisolvent Precipitation Method without Solvent Removal, Based on a Quality by Design (QbD) Approach

“…In this design, the experimental region is assumed to be a cube. The experiment is performed at the point corresponding to the midpoint of each axis and a repeated experiment is performed at the center of a multidimensional cube [25]. A total of 17 experiments were performed at three levels, with three factors.…”

Continuous Manufacturing of Homogeneous Ultralow-Dose Granules by Twin-Screw Wet Granulation

“…Since continuous technologies are heavily promoted by the authorities [7,8], intense R&D efforts are going into their possible industrial applications [9,10]. Numerous papers have been published based on the research conducted on Twin-Screw Granulators [11][12][13][14][15][16][17].…”

Analysis of Microstructure of Granules Prepared by Continuous Twin Screw Granulator Using X-Ray Micro-computed Tomography

“…Dhenge et al 8) studied binder viscosity on the granules properties. Vercruysee et al 9) and Liu et al 10) investigated the relationships between the process parameters of the TSG and the granule/tablet properties using design of experiments (DoE). El Hagrasy et al 11) investigated the effects of raw material properties on the granule properties and the granulation behavior.…”

“…Most of the previous studies focused on the investigation of granule properties prepared by the TSG under various operational conditions, and not many researchers have studied the tablet properties prepared from the TSG. 9,10) Regarding tablet properties, the tablet strength has been studied; however, drug dissolution from tablets, a major factor in the determination of the efficacy and safety of oral dosage forms, has not been well studied. Since tablets are the most commonly used oral dosage forms, research on the tablet properties prepared by the TSG is crucial for developing the pharmaceutical products.…”